Medical Breakthroughs in Psychiatry

There has been a series of articles implicating tryptophan metabolism in psychiatry (1, 2, 3). For many years serotonin was thought to be low in depression. However, the new findings are in a different pathway of tryptophan metabolism. The original theory was that tryptophan was being metabolized too slowly, causing a deficiency in serotonin. However, actual measurements indicate that tryptophan is being metabolized too rapidly!

There is also a strong theory involving the enzyme COMT (4). There is also a strong theory of mitochondrial dysfunction (5).

Treatments

Unfortunately the news is not all good news (8, 9). Very bad side effects have been reported from orthodox psychiatric treatments.

Diet

Ref. 10 shows a marked effect of diet on brain tryptophan and on serotonin synthesis. Carbohydrate increases the brain tryptophan.

"An 8-fold variation occurred in cortex tryptophan: a marked decline followed zein ingestion, and modest reductions after casein or gluten. A large rise in cortex tryptophan occurred after lactalbumin consumption, and smaller increases after soy protein or carbohydrate (no protein). In the brain regions examined, a 4-8-fold range in serotonin synthesis occurred which closely followed the tryptophan alterations."

Choi S, Disilvio B, Fernstrom MH, Fernstrom JD.

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh PA 15213, United States; Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh PA 15213, United States; Department of Psychology, University of Pittsburgh School of Medicine, Pittsburgh PA 15213, United States.

This quote is from Ref. 10, which used rats. Zein is a protein from corn, which is low in tryptophan. They did not test gelatin, which has no tryptophan. This report proves the importance of diet to the brain.

Unusual Theories

"The findings of this study indicate a hyperactive pro-inflammatory response inducing a change in tryptophan metabolism that might be related to the development of positive symptoms in schizophrenia." Kim YK, Myint AM, Verkerk R, Scharpe S, Steinbusch H, Leonard B. Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea.

This quote is from Ref. 12.
"The hyperactive inflammatory response system could induce enhanced tryptophan breakdown." Kim et al

Irritable Bowel Syndrome

There are many known physical diseases with psychiatric symptoms. An example is irritable bowel syndrome (13). The authors considered it a stress-related disorder.

"Both kynurenine levels and the kynurenine:tryptophan ratio were significantly increased in the IBS cohort compared with healthy controls." Clarke et al (13)

Orthomolecular Treatment

Orthomolecular theories and treatments have been described in great detail in the Associated Content references (14-20). My theory favors a low protein diet. Also carbohydrates are restricted in order to reduce the flooding of the brain with tryptophan.

Conclusions

A lot of brilliant discoveries have been made. They must now be translated into treatments. More research is still needed.

References

1. Two complex genotypes relevant to the kynurenine pathway and melanotropin function show association with schizophrenia and bipolar disorder.

Miller CL, Murakami P, Ruczinski I, Ross RG, Sinkus M, Sullivan B, Leonard S.

Schizophr Res. 2009 Jun 5. [Epub ahead of print]

2. Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder.

Miller CL, Llenos IC, Dulay JR, Weis S.

Brain Res. 2006 Feb 16;1073-1074:25-37. Epub 2006 Jan 30.

3. Alterations in kynurenine precursor and product levels in schizophrenia and bipolar disorder.

Miller CL, Llenos IC, Cwik M, Walkup J, Weis S.

Neurochem Int. 2008 May;52(6):1297-303. Epub 2008 Feb 2.

4. COMT genotype increases risk for bipolar I disorder and influences neurocognitive performance.

Burdick KE, Funke B, Goldberg JF, Bates JA, Jaeger J, Kucherlapati R, Malhotra AK.

Bipolar Disord. 2007 Jun;9(4):370-6.

5. Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL, Wayland M, Freeman T, Dudbridge F, Lilley KS, Karp NA, Hester S, Tkachev D, Mimmack ML, Yolken RH, Webster MJ, Torrey EF, Bahn S: Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress.

Mol Psychiatry 2004, 9(7):684-97, 643.

6. Raust A, Slama F, Mathieu F, Roy I, Chenu A, Koncke D, Fouques D, Jollant F, Jouvent E, Courtet P, Leboyer M, Bellivier F: Prefrontal cortex dysfunction in patients with suicidal behavior.

Psychol Med 2007, 37(3):411-419.

7. Differential association of the COMT Val158Met polymorphism with clinical phenotypes in schizophrenia and bipolar disorder.

Goghari VM, Sponheim SR.

Schizophr Res. 2008 Aug;103(1-3):186-91. Epub 2008 Jun 20.

8. Tako-tsubo cardiomyopathy following electroconvulsive therapy.

Chandra PA, Golduber G, Chuprun D, Chandra AB.

J Cardiovasc Med (Hagerstown). 2009 Apr;10(4):333-5.

9. Antidepressive-drug-induced bodyweight gain is associated with polymorphisms in genes coding for COMT and TPH1.

Secher A, Bukh J, Bock C, Koefoed P, Rasmussen HB, Werge T, Kessing LV, Mellerup E.

Int Clin Psychopharmacol. 2009 May 23. [Epub ahead of print]

10. Meal ingestion, amino acids and brain neurotransmitters: Effects of dietary protein source on serotonin and catecholamine synthesis rates.

Choi S, Disilvio B, Fernstrom MH, Fernstrom JD.

Physiol Behav. 2009 May 18. [Epub ahead of print]

11. Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia.

Yao JK, Dougherty GG Jr, Reddy RD, Keshavan MS, Montrose DM, Matson WR, Rozen S, Krishnan RR, McEvoy J, Kaddurah-Daouk R.

Mol Psychiatry. 2009 Apr 28. [Epub ahead of print]

12. Cytokine changes and tryptophan metabolites in medication-naïve and medication-free schizophrenic patients.

Kim YK, Myint AM, Verkerk R, Scharpe S, Steinbusch H, Leonard B.

Neuropsychobiology. 2009;59(2):123-9. Epub 2009 Apr 22.

13. Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort.

Clarke G, Fitzgerald P, Cryan JF, Cassidy EM, Quigley EM, Dinan TG.

BMC Gastroenterol. 2009 Jan 20;9:6.

14. www.associatedcontent.com/article/1817632/antipsychiatry_is_too_radical.html

15. www.associatedcontent.com/article/1810794/scientology_is_bogus.html

16. www.associatedcontent.com/article/1728112/mental_illness_and_homelessness.html
17. www.associatedcontent.com/article/1698919/advances_in_biological_psychiatric.html
18. www.associatedcontent.com/article/1680090/cuban_research_on_schizophrenia.html
19. www.associatedcontent.com/article/1680380/the_virus_theory_for_schizophrenia.html
20. www.associatedcontent.com/article/1676885/new_ideas_in_psychiatry.html